Diabetes is one of lifestyle-related diseases with the background of change of eating habit and lack of exercise. Hence, diet and exercise therapies are performed in patients with diabetes. Furthermore, when its sufficient control and continuous performance are difficult, drug treatment is simultaneously performed.
In recent years, development of various antidiabetic agents has been progressing with the background of a rapid increase of diabetic patients. For example, α-glucosidase inhibitors, which delay carbohydrate digestion and absorption at the small intestine, are used to improve postprandial hyperglycemia. However, since α-glucosidase inhibitors do not affect elevated blood glucose levels after ingesting glucose, which is one of monosaccharides (Journal of Japanese Society of Nutrition and Food Science, vol. 45, page 27, 1992), with recently changing components of carbohydrates in meals, it has been desired to develop agents which exert a wider range of activities inhibiting carbohydrate absorption.
In the meantime, it has been known that SGLT1, sodium-dependent glucose transporter 1, exists in the small intestine which controls carbohydrates absorption. It has also been reported that insufficiency of glucose and galactose absorption arises in patients with dysfunction due to congenital abnormalities of human SGLT1 (Supplementary Volume of Nippon Rinsho, Ryoikibetsu Shokogun 19, pages 555–556; Saishin Igaku, vol. 51, pages 84–90, 1996; Nippon Rinsho, vol. 55, no. 8, pages 249–257, 1997). In addition, it has been confirmed that SGLT1 relates to glucose and galactose absorption (Kidney and Dialysis, extra edition, pages 232–237, 1998; Nature, vol. 350, pages 354–456, 1991).
Furthermore, generally in diabetic patients, carbohydrate digestion and absorption are accelerated. For example, it is confirmed that mRNA and protein of SGLT1 increase and absorption of glucoses are accelerated in OLETF rats and Wistar-rats with streptozotocin-induced diabetic symptoms (Diabetologia, vol. 41, pages 1459–1466, 1998; Biochemical Society Transactions, vol. 25, page 479S, 1997).
Therefore, blocking a human SGLT1 activity inhibits absorption of carbohydrates such as glucose at the small intestine, subsequently can prevent increase of blood glucose level. Especially, it is considered that delaying carbohydrate absorption based on the above mentioned mechanism is effective to normalize postprandial hyperglycemia. In addition, since increase of SGLT1 in the small intestine is thought to contribute to increased carbohydrate absorption in diabetic patients, fast development of agents which have a potent inhibitory activity in human SGLT1 has been desired for preventing or treating diabetes.